Abstract Despite the expenditure of nearly 6% of Medicare funds on the care of patients with end stage renal disease, quality of life is poor and chronic pain present in the majority of the 511,000 maintenance dialysis patients in the United States. Evidence to guide pain control and the safe use of opioid narcotics in this population is scant, but opioids are nevertheless utilized by the majority of maintenance dialysis patients and are associated with greatly elevated risks of death, hospitalizations, fractures, and mental status changes. In response to the NIDDK HEAL Initiative: Integrated Approach to Pain and Opioid Use in Hemodialysis Patients: The Hemodialysis Opioid Prescription Effort (HOPE) Consortium (RFA-DK-18-030) and the clear need for data to better guide opioid use in hemodialysis patients, we propose the addition of New York University School (NYU) of Medicine as a HOPE consortium clinical center and the Pain and Opioids in End Stage Renal Disease risk reduction with Mindfulness and Buprenorphine (POEM-B) Trial: a 3-arm multi-site randomized trial. Approximately 600 hemodialysis patients receiving chronic opioids will be randomized across the HOPE consortium to enhanced treatment as usual, buprenorphine therapy, or buprenorphine plus mindfulness-based cognitive therapy intervention delivered by telephone and adapted for pain (MCBT-TP). The principal investigators and the co-Investigators at the NYU clinical center are deeply experienced in working with opioid patient populations and leading high-quality and collaborative NIH clinical trials in the hemodialysis population, mindfulness-based therapies, and opioid medication treatments. Furthermore, a local network including 20 free-standing dialysis units and more than 2900 dialysis patients will allow the NYU clinical center to recruit from a uniquely large source population representative of the diversity of race, ethnicity, gender and dialysis practice patterns across the United States. These investigators and resources will be leveraged to assess the following specific aims: Aim 1?To assess the effectiveness of buprenorphine in reducing chronic opioid use and prescriptions in hemodialysis patients on opioids at baseline, compared with an enhanced treatment as usual intervention and to assess the effectiveness buprenorphine in improving pain intensity, other quality of life measures, and hospitalizations; Aim 2?To assess the incremental effectiveness of a mindfulness-based cognitive therapy intervention delivered by telephone and adapted for pain (MBCT-TP) added to buprenorphine compared to buprenorphine alone on pain-interference with physical, social, and mental functioning, opioid use, pain intensity, other quality of life measures, hospitalizations, and mortality. The POEM-B study addresses a critical knowledge gap and will provide evidence that can be readily implemented into clinical care and that directly improves quality of life and patient-centered outcomes in a growing and high-risk population.